H5N1 is a highly pathogenic avian influenza virus that can cause severe disease and death in humans. H5N1 is spreading rapidly in bird populations world-wide and there is great concern that this virus will begin to transmit between people and cause a global pandemic catastrophe. Vaccines are the cornerstone strategy for combating avian flu but there are complex challenges facing us today including, (1) the inability to manufacture the vast numbers of safe and effective doses needed to prevent infection on a world-wide scale;(2) the fact that the current vaccines are ineffective and require large doses, and (3), virus strains are continually changing, which complicates vaccine strain selection. TRIA Bioscience Corp. is developing a novel adjuvanted vaccine for pandemic H5N1 Flu that should solve many of the scientific and technological barriers confronting this field. The vaccine antigen is recombinant H5 haemagglutinin (rH5), which uses a production process that simplifies many of the manufacturing issues associated with conventional vaccines, and the adjuvant (GLA-SE) that combines two clinically-validated strategies for augmenting vaccine performance, a synthetic Toll-Like Receptor-4 agonist, GLA, and an oil-in-water emulsion, SE. We are building on our compelling Phase I SBIR data by proposing activities leading up through an IND. First, we will compare GLA-SE activity against two simpler GLA-formulations designed to streamline adjuvant development and regulatory approval. Second, we will establish vaccine protection in ferret challenge models and establish safety and immunogenicity end-points in non-human primates. Third, we will manufacture and release cGMP-grade H5 protein and adjuvant, and obtain FDA clearance for a Phase I clinical trial. The results from this study will provide a relevant measure of dose sparing for vaccine manufacturers and inform clinicians about a new tool for inducing broad immunity against drifted strains of H5N1 virus. The US and world governments are investing billions of dollars in pandemic preparedness measures and TRIA will be well-positioned to participate in this market. This vaccine's design is broadly applicable to other infectious diseases, which increases its commercial potential even further. PUBLIC HEALTH RELEVANCE: There is great international concern that the highly pathogenic H5N1 avian influenza virus will cause a pandemic infection resulting in millions of deaths. We are developing an adjuvanted vaccine with new technologies that will streamline manufacturing constraints and prevent H5N1 infection on a global scale.